Objectives: Sepsis or endotoxemia causes diaphragmatic dysfunction, which m
ay contribute to respiratory distress. Toxic free radicals are partly respo
nsible for the pathogenesis, Lidocaine scavenges the reactive molecules. Th
e purpose of the current study was to examine whether lidocaine prevents th
e diaphragmatic dysfunction of sepsis.
Design: Prospective, randomized animal study.
Setting: University research laboratory. Subjects: A total of 40 male Golde
n-Syrian hamsters.
Interventions: The animals were randomly allocated to one of five groups (n
= 8 each): hamsters undergoing sham laparotomy alone and receiving saline
infusion (Sham group), those undergoing cecal ligation with puncture (CLP)
and receiving an infusion of saline (Sepsis group), those undergoing sham l
aparotomy and receiving infusion of lidocaine, 2 mg/kg/hr (Sham-LID group),
those undergoing CLP and receiving infusion of lidocaine, 1 mg/kg/hr (Seps
is-LID 1 group), and those undergoing CLP and receiving infusion of lidocai
ne, 2 mg/kg/hr (Sepsis-LID 2 group). Subcutaneous infusion of saline or lid
ocaine was started 6 hrs before surgery and continued until 24 hrs after th
e operation when all hamsters were killed.
Measurements and Main Results: Diaphragmatic contractility and fatigability
were assessed in vitro by using muscle strips excised from the costal diap
hragms, Diaphragmatic levels of malondialdehyde (MDA), an index of free rad
icals-mediated lipid peroxidation, were also measured. Twitch and tetanic t
ensions in the Sepsis group were reduced compared with the Sham group, Tens
ions generated during fatigue trials were decreased, and MDA levels were el
evated in diaphragms from the Sepsis group. An infusion of 2 mg/kg/hr lidoc
aine attenuated contractile dysfunction, aggravation of fatigability, and t
he increase in MDA formation. In contrast, 1 mg/kg/hr lidocaine failed to d
o so, Electrophysiologic diaphragmatic characteristics in the Sham-LID grou
p were similar to those in the Sham group.
Conclusions: Pretreatment with 2 mg/kg/hr but not 1 mg/kg/hr lidocaine atte
nuated sepsis-induced diaphragmatic dysfunction in hamsters assessed by con
tractile profiles and endurance capacity, This beneficial effect of lidocai
ne may be attributable, in part, to inhibition of lipid peroxidation in the
diaphragm.